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One of PCORI’s core priorities is funding research that can improve the health of underserved populations. That includes people who are transgender—an umbrella term describing individuals whose gender identity differs from the sex they were assigned at birth—because they are at higher risk for mental and physical health problems compared with peers who are not transgender. The estimated 1 million transgender people in the United States also have been underrepresented in research.


View Evidence Updates for clinicians and patients that discuss research findings on the cardiovascular risks of estrogen use in transgender women.

In response, a PCORI-funded project based at Emory University has examined the risks of gender affirmation therapies, such as estrogen treatment for transgender women. Care guidelines for estrogen therapy for transgender women are loosely based on treatments for postmenopausal women. A new paper that the researchers have published in Annals of Internal Medicine reports that, compared with women and men of the same age and ethnic background who are not transgender, transgender women who receive estrogen treatments face a higher risk for stroke and dangerous blood clots, particularly two to six years after initiating therapy.

This finding differs from earlier results of smaller studies, including those the World Professional Association for Transgender Health has drawn on in developing care standards. Those studies suggested an elevated risk for stroke and blood clots only in the first two years after the start of treatment. The PCORI-funded study suggests that patients undergoing hormone therapy treatment need to understand the potential risks, and it also suggests that more research is needed. (See box, A Clinician’s View.)


To provide more context for this important work, we spoke with the study’s lead researcher, Michael Goodman, MD, MPH, and Savannah Winter, a transgender woman on the project’s advisory board.

Ms. Winter, can you describe your experience with hormone therapy?

A Clinician’s View

Vin Tangpricha, MD, PhD, is an endocrinologist and Professor of Medicine at Emory University, and a coauthor of the new paper. He is also President-Elect of the World Professional Association for Transgender Health.

“This study is the largest cohort of transmasculine and transfeminine people in the United States. It is important to keep in mind that transgender health is a relatively new, albeit rapidly growing, field of research. High-quality data are still lacking with respect to many critical gaps in knowledge.

“Closing these knowledge gaps will require larger, more in-depth studies performed independently by different institutions and in a variety of settings. For example, additional research is needed to delineate what factors such as type of estrogen, route of administration, dose, and combination with other medications may explain the observed risks, and how these risks can be mitigated.

“In the meantime, findings from this study will be considered in the next version of the WPATH Standards of Care, which are currently in revision."

Savannah Winter: I’m 29. I started seeking care for gender dysphoria when I was 19, but I didn’t get hormone therapy until I was 24. I do transdermal hormone therapy, which is through a patch. When I started, I was concerned about health outcomes, but my real priority was mitigating risks. I knew that the therapy would improve my outcomes drastically, especially my psychological outlook.

I needed to address my dysphoria. It was a general unease in the skin I’m in. I have a variety of other issues—depression, anxiety—and having the dysphoria on top of that made everything worse. Treating my dysphoria through my gender transition has helped a lot. Depression causes body pains, and now I ache less. I feel more motivated to do things, and I have one less thing pulling me down. In general, I’m able to be myself. I don’t feel trapped in something suffocating and restrictive.

Dr. Goodman, what makes this study different from previous research?

Michael Goodman: Numbers—and the use of a reference group from the same population. Most studies of transgender people are done in clinics that specialize in transgender care. They don’t have individuals who are not transgender to make comparisons, whereas we had the total membership of Kaiser Permanente at our research sites in Georgia and California.

We identified thousands of transgender people and then matched them against people in similar groups—such as age, ethnicity, or geographic area—who are not transgender. We then compared risk levels for cardiovascular events.

Using health records, we found patterns that were different from previous studies, including risks that were not that high initially but increased after two to six years of hormone use. We don’t know whether the risk continues to go up because we don’t have the longer-term data yet. 

It sounds like more research is needed to address those questions.

Michael Goodman: Absolutely. We don’t know whether certain regimens of hormone therapy are driving this elevated risk. Determining that will be very important. The take-home message is doctors who prescribe hormone therapy should not relax oversight after two years, which would have been conventional wisdom.

And hormone therapy is just one aspect of transgender health that requires more research. You have to have data on transgender people to draw conclusions or provide recommendations about care.

I know it is anxiety-inducing for researchers to take one hand off the steering wheel and let someone else grab it, but it is worth it for everyone.

Savannah Winter Stakeholder Partner

What role did stakeholders play throughout the project?


Compared with women who are not transgender, transgender women had an elevated risk for venous thromboembolism (VTE), a dangerous type of blood clot, particularly six to eight years after hormone treatment began. 
Credit: Annals of Internal Medicine

Michael Goodman: We started drawing on expertise of people who are transgender and doctors who specialize in transgender care while preparing our research proposal. This was done by circulating an online survey asking stakeholders to rank research questions and suggest some of their own. The question of cardiovascular problems—and especially blood clots, which is the subject of this paper—was high on their priority list.

To assemble a stakeholder advisory group, we identified physicians at each of our four research sites who specialize in transgender care, and asked them to nominate patients. We ended up with a group that was just wonderful.

I come from cancer research, so that would have been my natural direction in research, but we learned from our advisors that there were more-immediate needs. The stakeholders had real examples of cardiovascular problems in their community, and they felt it was important for us to look into this. They also helped us in a myriad of other ways, from teaching us about correct terminology to assisting in data collection and helping interpret study results. I cannot overstate how important their input was.

Savannah Winter: The researchers really worked with us. They listened to us and considered everything we said, sometimes to the extent that they had to go back to the drawing board.

Community-focused research has been a boon to the point that it should be looked at as a general model. I know it is anxiety-inducing for researchers to take one hand off the steering wheel and let someone else grab it, but it is worth it for everyone.

The views expressed here are those of the authors and not necessarily those of PCORI.

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